Circularly Polarized Luminescence of Achiral Cyanine Molecules

Am. Chem. Soc.2019141249490-9494. Publication Date (Web):June 7, 2019 ... Experimental section, extra figures and results (PDF) ... University of ...
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Circularly Polarized Luminescence of Achiral Cyanine Molecules Assembled on DNA Templates Qiao Jiang,†,# Xuehui Xu,†,# Ping-An Yin,⊥,□ Kai Ma,†,‡ Yonggang Zhen,⊥ Pengfei Duan,⊥,‡ Qian Peng,*,⊥ Wei-Qiang Chen,¶ and Baoquan Ding*,†,‡,§

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CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China § School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China ⊥ Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing 100190, China ¶ Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou 730000, China □ South China University of Technology, 381 Wushan Road, Guangzhou 510641, China S Supporting Information *

transferring properties have been described. These complexes offer an alternative method for fabricating CPL materials.8−11 It has been found that monodispersed chiral gelators are able to self-assemble into nanostructures with achiral fluorophores, showing supramolecular chirality transfer and circularly polarized luminescent emission.9−11 Fluorophores exhibiting aggregation-induced emission (AIE) are of interest for their light-emitting properties.12,13 AIE concepts have been introduced in the design and fabrication of CPL materials.14−16Alternatively, self-assembled supramolecular techniques have been utilized in the fabrication of circularly polarized luminescent hydrogel with AIE dyes.11 The preparation of these supramolecular hydrogels requires organic solvents, which may limit the wide application of this strategy, especially in biological systems. Natural chiral molecules such as DNA exhibit chirality strongly tied to their structures.17 The circular dichroism (CD) signals of DNA generally appear in the ultraviolet range.18 CPL can be induced by pyrene π-stack arrays formed on chemically modified DNA double helical structures, but laborious synthetic procedures are required to obtain this modified molecule.19 We hypothesized that DNA molecules would behave as a unique chiral template for fluorophore binding: that DNA’s natural chirality can be transferred to the bound dye molecules, triggering CPL activity from the coassemblies. However, conventional DNA-binding dyes suffer from aggregation-caused quenching (ACQ) of luminescence, which would be expected to result in a severely compromised CPL signal.11,20 An alternative choice of dye is from a series of carbazole-based cyanine molecules, which are reported to exhibit weak emission when they are present monomolecularly in aqueous solution but switch to a strong emission state after binding to DNA duplexes.21 The electrostatic interaction between the ammonium cations of the biscyanine molecules and the phosphate anions of DNA helix backbone lead to the anchoring of fluorophores to the minor groove of the DNA

ABSTRACT: The exploration of biocompatible materials with circularly polarized luminescence (CPL) activity is becoming an attractive topic due to the great potential application in biosensing and bioimaging. Here, we describe a strategy to fabricate new CPL-active biomaterials using achiral carbazole-based biscyanine fluorophores coassembled with chiral deoxyribonucleic acid (DNA) molecules. This cyanine molecule has been shown to behave as a DNA detecting probe, featuring strong fluorescent emission induced by restriction of intramolecular rotation (RIR). When the achiral cyanine molecules are bound to the minor groove of DNA via electrostatic attraction in aqueous solution, the chirality of the DNA molecules can be transferred to the confined RIR cyanine dyes, triggering a remarkable circularly polarized luminescent emission. The chirality of the CPL signal can be regulated by the structures of the DNA templates. Stimuli-responsive CPL activates were observed from DNA−cyanine complexes. We further verified this strategy on different DNA-based nanomaterials, including DNA origami nanostructure. Our design presents a new avenue to fabricate compatible CPL materials.

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he phenomenon of circularly polarized luminescence (CPL) arising from chiral fluorophores or supramolecular systems has been a focus of burgeoning research in recent years. CPL is usually generated from molecules or composites with both chirality and fluorescent emission.1,2 There has been strong interest around the design and fabrication of novel CPL materials for their potential applications in sensors, chiroptical materials, and photoelectric devices.3−6 One way to obtain CPL materials is to synthesize chiral molecules or nanoparticles with fluorescent properties.1,2 For example, cadmium selenide quantum dots (CdSe QDs) can be decorated with Land D-cysteines.7 These Cys-CdSe QDs show distinct electronic circular dichroism (CD) and CPL signals. In addition, self-assembled supramolecular systems with the chiral © 2019 American Chemical Society

Received: April 3, 2019 Published: June 7, 2019 9490

DOI: 10.1021/jacs.9b03305 J. Am. Chem. Soc. 2019, 141, 9490−9494

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Journal of the American Chemical Society double helix. The restricted intramolecular rotational (RIR) motions, an important feature of AIE-active dyes, of bound carbazole-based cyanine molecules cause a large reduction in the nonradiative decay and induce a strong enhancement of the emission.21 Here, we demonstrated that DNA molecules can work as templates for the fabrication of CPL materials in aqueous solution. We constructed DNA duplexes and DNA origami nanostructures as the chiral templates for coassembly with achiral biscyanine molecules that possess a characteristic RIR emission. We observed the induced CPL signals of the DNA− cyanine complexes and found that the chirality of the CPL is dependent on the chirality of the DNA templates (Figure 1).

Figure 1. Schematic illustration of DNA−biscyanine hybrid CPLactive materials.

Figure 2. CPL spectra of DNA−biscyanine fabricated with (a, b) ssDNA or dsDNA and (c, d) DNA of differing GC contents. (e) Geometrical optimized DNA−biscyanine assemblies. (f) Mapped electrostatic potentials of the biscyanine monomer and DNA− biscyanine assembly. (g, h) CPL spectra of biscyanine loaded in pH switchable DNA templates.

The carbazole-based biscyanine (Figure 1) with RIR emission was synthesized based on fused aromatics; this molecule has been reported to be a sensitive electron donor for DNA detection.21 The biscyanine molecules were incubated with the single stranded (30 nt) or duplex (30 bp) DNA at room temperature for 30 min to form self-assembled chiral DNA−cyanine composites (Figure 2a). The cyanine exhibited a broad UV absorption spectrum and a weak fluorescent emission (peak: 600 nm) when dissolved in 1× annealing buffer (Figure S1). After DNA−biscyanine nanocomposite formation, a dramatic increase in the fluorescence intensity and a significant blueshift of the peak were observed, demonstrating cyanine’s RIR motions when bound to the DNA molecules (Figure S1). The dsDNA−cyanine composites showed absorptive intensity and fluorescence enhancement higher than those of ssDNA−cyanine, indicating a stronger interaction between the DNA duplex and the RIR molecules. The assembled DNA−biscyanine exhibited molecular chirality that was confirmed by the CD (Figure S2) and CPL measurements (Figure 2b). The confinement of biscyanine on DNA duplex induced CPL with an emission ranging from 480−750 nm. We examined duplex DNA templates of different guanine− cytosine composition (0, 40, and 80% GC contents) after incubation with biscyanine using fluorescence and CPL measurements (Figure 2c). As shown in Figures S3, S4, and 2d, DNA duplex−biscyanine assemblies exhibited a progressive enhancement of fluorescence intensity together with CPL emission upon decreasing the GC contents of the DNA. This

finding is in agreement with previous reports, which demonstrated that biscyanine dyes selectively bind to ATrich dsDNA.21 Stronger CD and CPL signals were observed from DNA−cyanine complexes with longer DNA duplex templates (Figure S5). To provide more insight of DNA−biscyanine interaction, the theoretical calculations were performed using hybrid quantum mechanism and molecular mechanism (QM/MM) method (see the computational details in Supporting Information) The geometrical optimization results revealed that positively charged biscyanine molecules selectively bind to AT-rich minor groove sites on double-stranded DNA (Figure 2e). The calculated CPL spectra (Figure S6a) were gradually increased in intensity from the unloaded biscyanine to 80% GC−DNA duplex−biscyanine to 40% GC−DNA duplex− biscyanine, which are in good agreement with the experimental observations. To analyze the molecular interactions, we examined the electrostatic and dispersion interaction characters in DNA−biscyanine, respectively. Compared to free biscyanine molecule, biscyanine in the minor groove of the DNA duplex showed more positive charges in the binding position (Figure 2f). The van der Waals largely contribute to the dispersion interactions of DNA−biscyanine (Figure S6b). We employed DNA-based nanoswitches, whose conformational changes can be triggered by specific pH windows,22 as 9491

DOI: 10.1021/jacs.9b03305 J. Am. Chem. Soc. 2019, 141, 9490−9494

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Journal of the American Chemical Society

Figure 3. Optical characterization of DNA duplex−biscyanine enantiomeric pairs. (a) Scheme of D- and L-d[A]10:d[T]10 DNA duplex−biscyanine nanocomposites. (b) Images of biscyanine solution and DNA duplex solutions after biscyanine loading under UV irradiation. (c) Fluorescence spectra of enantiomeric pairs of Dand L-DNA duplexes after coassembly with RIR biscyanine molecules. (d) Fluorescence decay of the unloaded RIR molecules and the DNA−biscyanine enantiomeric pairs. (e) Mirror CPL spectra of enantiomeric pairs of D- and L-DNA duplex−biscyanine. (f) CPL spectra of the enantiomeric pairs under cyclical thermal treatment.

Figure 4. Optical characterization of CPL-active DNA origami. (a) Schemes and AFM images of DNA origami and origami−cyanine nanoassemblies. (b) Agarose gel of M13 DNA, DNA origami, and origami−biscyanine. (c) Fluorescence spectra and (d) CPL spectra of free biscyanine, DNA origami, and DNA origami after biscyanine loading.

assembly templates. Through the formation of a Watson− Crick duplex and a pH-sensitive Hoogsteen parallel interactions (Figure 2g), these switchable DNA strands fold into intramolecular triplex structures with the relative content of TAT/CGC triplets in the DNA switches determining the pH responsive ranges.22 We chose two different nanoswitches for RIR molecule loading: one was a switch containing only TAT triplets (100% TAT) whose closing/opening structures can be triggered at pH 8/11, and another was a 50% content of TAT switch (50% TAT) that folds into triplex in an acid environment (pH 5) and unfolds at a mild basic pH (pH 8). As shown in Figure S7, the CD spectra (320−600 nm) of 100% TAT triplet−biscyanine exhibited increased chiral signals from pH 8 to 11. The switchable CPL emissions of 100% TAT triplet−biscyanine were also tuned to the specific pH window, indicating the triplex-to-duplex transition under basic pH conditions (Figure 2h). Similar tunable chiroptical signals were obtained with the 50% TAT triplet−biscyanine composites (Figure S8) when the DNA templates underwent the duplex-to-triplex transition from pH 8 to pH 5. These data demonstrate that the switching chiroptical properties of DNA triplet−biscyanine assemblies depends on the conformational changes of the DNA templates. Note that weaker CD and CPL responses were obtained when the DNA switches were triggered to form triplex structures, while no signal changes were observed from pH-unsensitive DNA duplexes (Figure S9). It is probably because of the weaker interactions of the RIR molecules with triplex DNA structures.

Next, D-DNA and L-DNA d[A]10:d[T]10 were annealed and used for assembly with biscyanine (Figure 3a). We estimated the loading content of the biscyanine with d[A]10:d[T]10 DNA duplexes as shown in Figure S10. Both enantiomeric DNA duplex−biscyanine solutions exhibited a strong fluorescent emission (Figure 3b, c). The fluorescence lifetime of biscyanine molecules in 1× annealing buffer was 0.7 ns. After assembly into DNA duplex, the fluorescence lifetimes of both DNA duplex−biscyanine nanocomposites were remarkably extended to 2.5 ns (Figure 3d). The D-and L-DNA duplex− biscyanine composites exhibited enantiomeric CD spectra (Figure S11). Figure 3e shows the CPL emissions of the two nanocomposites with different handedness. The calculated value of the dissymmetry factor (|glum|) of the CPL signal is ∼1.7 × 10−3. The results demonstrate the handedness of DNA−cyanine complex is dependent on the handedness of DNA template. The reversibility of the DNA−biscyanine enantiomeric pairs was investigated after multiple cycles of annealing (Figure 3f). By alternating between 80 and 25 °C, the switchable structural changes of the DNA−cyanine nanocomposites were achieved. As a result of thermalcontrolled hybridization and dissociation of the DNA−cyanine nanocomposites, cyclical changes in the CPL intensity were observed (Figure 3f). We also used DNA origami23 as a template for biscyanine loading. Before and after biscyanine binding, the nanostruc9492

DOI: 10.1021/jacs.9b03305 J. Am. Chem. Soc. 2019, 141, 9490−9494

Communication

Journal of the American Chemical Society

China (21721002), National Basic Research Programs of China (2016YFA0201601, 2018YFA0208900), the Key Research Program of Frontier Sciences, CAS, Grant QYZDB-SSW-SLH029, and the K. C. Wong Education Foundation.

tures were investigated by atomic force microscopy (AFM) and agarose gel electrophoresis (AGE). In the AFM images, bare DNA origami squares and biscyanine-loaded DNA nanostructures were both around 90 × 60 × 2 nm with uniform morphology (Figure 4a). In the ethidium bromide (EB)-free agarose gel images, only biscycanine-loaded squares showed a sharp band with a potent yellow fluorescence under UV irradiation, indicating that biscyanine molecules were coassembled into the DNA origami nanostructures (Figure 4b). After EB staining, the bare DNA origami became visible, migrating to almost the same position as the DNA origami− biscyanine (Figure 4b). The DNA origami−biscyanine nanocomplex exhibited strong fluorescence with an emission maximum around 550 nm (Figure 4c). The nanocomplex also demonstrated clear CD spectrum at 320−600 nm (Figure S12) and a CPL emission with the peak at 550 nm (Figure 4d), indicating that the chirality transferred from the chiral DNA nanostructures to the bound RIR molecules. In summary, assembly of achiral biscyanine dyes on chiral DNA molecules is a promising approach for fabricating CPLactive materials. DNA duplexes and origami nanostructures can be used as chiral templates for the incorporation of achiral biscyanine dyes. After RIR molecules are confined in the minor groove of the DNA double helical structures, a chirality transfer occurs, which can then be acquired by the loaded biscyanine molecules, triggering desirable and remarkable CPL emissions. Reversible CPL responses can be controlled by cyclic thermal treatments. We anticipate that other AIE molecules that can bind to DNA with different emission wavelengths can be used for coassembly with DNA templates to achieve tunable CPL activity.24,25 Our biomolecule-based CPL-active system shows great potential for use as CPL materials in biological studies. We envision that DNA-based CPL-active nanoassemblies with tunable optical properties will provide novel platforms for engineering functional chiroptical materials.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.9b03305. Experimental section, extra figures and results (PDF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Authors

*[email protected] *[email protected] ORCID

Pengfei Duan: 0000-0002-5971-7546 Qian Peng: 0000-0001-8975-8413 Baoquan Ding: 0000-0003-1095-8872 Author Contributions #

Q.J. and X.X. contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Grants 21573051, 31700871, and 51761145044), the Science Fund for Creative Research Groups of the National Natural Science Foundation of 9493

DOI: 10.1021/jacs.9b03305 J. Am. Chem. Soc. 2019, 141, 9490−9494

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DOI: 10.1021/jacs.9b03305 J. Am. Chem. Soc. 2019, 141, 9490−9494